[Show abstract][Hide abstract] ABSTRACT: Introduction: Dynamic susceptibility-weighted contrast-enhanced magnetic-resonance-imaging (DSC-MRI) is used to assess penumbral flow in acute ischemic stroke. However, validated automated post-processing methods are lacking. For these, the choice of the arterial input function (AIF) is a major confounder, and has not been validated so far by an imaging gold-standard. Materials and Methods: In 18 (sub)acute stroke patients with MRI and H 2 O 15 positron-emission-tomography (PET) performed at the Max-Planck-Institute in Cologne, the optimal AIFs were calculated based on the kinetic model of DSC-MRI customly adapted to individual PET and MRI data. Cerebral-blood-flow (CBF), cerebral-blood-volume (CBV), mean-transit-time (MTT) and time-to-maximum (Tmax) were computed applying 3 methodologies: 1) GLOBAL AIF: One median AIF. 2) CLUSTER AIF: A cluster analysis approach identified voxels with similar AIFs. 3) MANUAL AIF selection. Non-deconvolved Time-to-peak (TTP) maps were created. All maps were tested for their performance in penumbral flow detection (<20ml/100g/min) on a voxel level by receiver operating characteristics (ROC) curve analysis. Results: Optimal PET validated AIF curves showed a wide distribution, suggesting that one single AIF for all voxels of one patient might not be adequate. Accordingly, the GLOBAL AIF methodology performed similarly (AUC 0.72-0.85) to MANUAL AIF (AUC 0.73-0.85). CLUSTER AIF, however, as a multiple-AIF approach, showed significantly better performance (AUC 0.82-0.90), surpassing even the high performance of TTP (AUC 0.87). Discussion: Our results challenge the widely used Global AIF approach. The CLUSTER AIF concept was superior over single voxel approaches and over TTP. The findings support multiple-AIF approaches and might enhance the performance of deconvolved parameters.
European Stroke Organization (ESO) Conference, Glasgow, UK; 04/2015
[Show abstract][Hide abstract] ABSTRACT: In acute stroke, the DWI-FLAIR mismatch allows for the allocation of patients to the thrombolysis window (<4.5 hours). FLAIR-lesions, however, may be challenging to assess. In comparison, DWI may be a useful bio-marker owing to high lesion contrast. We investigated the performance of a relative DWI signal intensity (rSI) threshold to predict the presence of FLAIR-lesions in acute stroke and analyzed its association with time-from-stroke-onset.
In a retrospective, dual-center MR-imaging study we included patients with acute stroke and time-from-stroke-onset ≤12 hours (group A: n = 49, 1.5T; group B: n = 48, 3T). DW- and FLAIR-images were coregistered. The largest lesion extent in DWI defined the slice for further analysis. FLAIR-lesions were identified by 3 raters, delineated as regions-of-interest (ROIs) and copied on the DW-images. Circular ROIs were placed within the DWI-lesion and labeled according to the FLAIR-pattern (FLAIR+ or FLAIR-). ROI-values were normalized to the unaffected hemisphere. Adjusted and nonadjusted receiver-operating-characteristics (ROC) curve analysis on patient level was performed to analyze the ability of a DWI- and ADC-rSI threshold to predict the presence of FLAIR-lesions. Spearman correlation and adjusted linear regression analysis was performed to assess the relationship between DWI-intensity and time-from-stroke-onset.
DWI-rSI performed well in predicting lesions in FLAIR-imaging (mean area under the curve (AUC): group A: 0.84; group B: 0.85). An optimal mean DWI-rSI threshold was identified (A: 162%; B: 161%). ADC-maps performed worse (mean AUC: A: 0.58; B: 0.77). Adjusted regression models confirmed the superior performance of DWI-rSI. Correlation coefficents and linear regression showed a good association with time-from-stroke-onset for DWI-rSI, but not for ADC-rSI.
An easily assessable DWI-rSI threshold identifies the presence of lesions in FLAIR-imaging with good accuracy and is associated with time-from-stroke-onset in acute stroke. This finding underlines the potential of a DWI-rSI threshold as a marker of lesion age.
PLoS ONE 03/2014; 9(3):e92295. DOI:10.1371/journal.pone.0092295 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In acute symptomatic vertebrobasilar artery stenosis, the use of mechanical recanalisation remains controversial. The complication rate of acute interventional recanalisation (aIR) has to be considered, as evidence from randomised trials is lacking. In a single centre retrospective case series, we here describe complications and outcome after aIR.
We retrospectively assessed aIR in a tertiary care centre and included the following parameters: indication for aIR, national institute of health stroke scale (NIHSS) score on admission, recanalisation by thrombolysis in myocardial infarction score (TIMI) grades, post-interventional complications, mortality, NIHSS and modified Rankin scale at follow-up and rate of restenosis.
We identified 14 aIR (14 percutaneous transluminal angioplasty with or without stent implantation in 12 patients; 6/12 with thrombolysis; n = 6 vertebral artery, n = 8 basilar artery; 4 women, mean age 67 years). Mortality was 25 % (3/12) after 7 days and 42 % (5/12) after 12 months. In 12/14, interventions are complete (TIMI 3, 86 %), in 2/14, a partial recanalisation (TIMI 2, 14 %) was achieved. In one case, a peri-interventional fatal intracerebral haemorrhage occurred (1/12, 8 %). At late follow-up (mean 342 days), one re-occlusion (1/7, 14 %) and one recurrent stroke (1/12, 8 %) were observed.
In our single centre series of vertebrobasilar aIR recanalisation rate was high. However, procedural safety and clinical outcome varied considerably. The results of aIR need to be assessed in multicentric registers to define the procedural risk and outcome in the clinical setting.
[Show abstract][Hide abstract] ABSTRACT: Perfusion-weighted imaging maps are used to identify critical hypoperfusion in acute stroke. However, quantification of perfusion may depend on the choice of the arterial input function (AIF). Using quantitative positron emission tomography we evaluated the influence of the AIF location on maps of absolute and relative perfusion-weighted imaging to detect penumbral flow (PF; <20 mL/100 g/min on positron emission tomography(CBF)) in acute stroke.
In 22 patients with acute stroke the AIF was placed at 7 sites (M1, M2, M3 ipsi- and contralateral and internal carotid artery-M1 contralateral to the infarct). Comparative (15)O-water positron emission tomography and AIF-dependent perfusion-weighted imaging (cerebral blood flow, cerebral blood volume, mean transit time, and time to maximum) were performed. A receiver operating characteristic curve analysis described the threshold independent performance (area under the curve) of the perfusion-weighted maps for all 7 AIF locations and identified the best AIF-dependent absolute and relative thresholds to identify PF. These results were compared with AIF-independent time-to-peak maps.
Quantitative perfusion-weighted imaging maps of cerebral blood flow and time to maximum performed best. For PF detection, AIF placement did significantly influence absolute PF thresholds. However, AIF placement did not influence (1) the threshold independent performance; and (2) the relative PF thresholds. AIF placement in the proximal segment of the contralateral middle cerebral artery (cM1) was preferable for quantification.
AIF-based maps of cerebral blood flow and time to maximum were most accurate to detect the PF threshold. The AIF placement significantly altered absolute PF thresholds and showed best agreement with positron emission tomography for the cM1 segment. The performance of relative PF thresholds, however, was not AIF location-dependent and might be along with AIF-independent time-to-peak maps, more suitable than absolute PF thresholds in acute stroke if detailed postprocessing is not feasible.
[Show abstract][Hide abstract] ABSTRACT: Supported by results of the ECASS III study, intravenous rt-PA thrombolysis is considered a standard therapy for acute stroke within 4.5 h. Still under debate is the use of a more aggressive treatment as that of local intraarterial thrombolysis (LIT) or combining intravenous administration of recombinant tissue plasminogen activator (rt-PA) followed by LIT (bridging concept). Mechanical thrombus removal devices and effective flow achievement by stenting are reported to increase the recanalization rate and patient outcome. Newer reports showed the use of intracranial stents as the latest trend-setting technique. A combined approach hereby appears to achieve the best results consisting of pharmacologic thrombolysis, manual aspiration devices and stenting. We employed a novel removable stent as a new approach in acute stroke, aiming to make the intraarterial thrombolysis through an enhanced thrombus contact surface more effective and to reduce the effective revascularisation time with the possibility of stent removal after re-opening the occluded vessel.
We describe four cases with acute stroke in the anterior and posterior circulation using a newer self-expandable removable stent (Solitaire™ AB) combined with LIT performed in the 'bridging technique', occasionally supported by additional thrombus aspiration.
In all cases, we directly achieved after stenting an effective revascularization with fast recanalization time when using stent implantation first. Stenting was always technically successful without complications.
The easy handling of a removable stent in stent-assisted revascularization combined with thrombolysis (i.v./i.a.) is a newly described technique for acute stroke treatment, which join immediate mechanical recanalization, postulated improved thrombolysis and the possibility of stent removing.
[Show abstract][Hide abstract] ABSTRACT: Perfusion-weighted imaging-derived maps of time-to-maximum (Tmax) are increasingly used to identify the tissue at risk in clinical stroke studies (eg, DEFUSE and EPITHET). Using quantitative positron emission tomography (PET), we evaluated Tmax to define the penumbral flow threshold in stroke patients and compared its performance to nondeconvolved time-to-peak (TTP) maps.
Comparative perfusion-weighted imaging and quantitative 15O-water PET images of acute stroke patients were analyzed using cortical regions of interest. A receiver-operating characteristic curve analysis described the threshold independent performance of Tmax (area under the curve) and identified the best threshold (equal sensitivity and specificity threshold) to identify penumbral flow (< 20 mL/100 g/min on PET cerebral blood flow). The results were compared with nondeconvolved TTP and other current perfusion-weighted imaging maps using the Mann-Whitney rank-sum test.
In 26 patients (time delay between MRI and PET, 65 minutes), the best threshold for penumbral flow was 5.5 seconds for Tmax (median; interquartile range, 3.9-6.6; sensitivity/specificity, 88%/89%). The area under the curve value was 0.95 (median; interquartile range, 0.93-0.97). Deconvolved Tmax did not perform significantly better than TTP (P = 0.34).
Maps of Tmax detected penumbral flow but did not perform better than the easy-to-obtain maps of nondeconvolved TTP. Thus, "simple" TTP maps still remain suitable for clinical stroke studies if detailed postprocessing is not feasible.
[Show abstract][Hide abstract] ABSTRACT: Perfusion-weighted (PW) MRI is increasingly used to identify the tissue at risk. The adequate PW-MRI map and threshold remain controversial due to a considerable individual variation of values. By comparative positron emission tomography, we evaluated a simple MR-based and positron emission tomography-validated calibration of PW maps.
PW-MRI and quantitative positron emission tomography (15O-water) of patients with acute stroke were used to calculate averaged as well as individual thresholds of penumbral flow (positron emission tomography cerebral blood flow (<20 mL/100 g/min) for maps of time to peak, mean transit time, cerebral blood flow, and cerebral blood volume. A linear regression analysis studied the variability of the individual thresholds using 3 different PW reference regions (hemispheric, white matter, gray matter). The best model was used for volumetric analysis to compare averaged and scaled individual thresholds and to calculate look-up tables for PW maps.
In 26 patients, the averaged thresholds were (median/interquartile range): cerebral blood flow 21.7 mL/100 g/min (19.9 to 32); cerebral blood volume 1.5 mL/100 g (0.9 to 1.8); mean transit time seconds 5.2 (3.9 to 6.9); and relative time to peak 4.2 seconds (2.8 to 5.8). The large individual variability was best explained by the mean value of the hemispheric reference derived from a region of interest on a level with the basal ganglia of the unaffected hemisphere (R(2): cerebral blood flow 0.76, cerebral blood volume 0.55, mean transit time 0.83, time to peak 0.95). Hemispheric reference-corrected thresholds clearly improved the detection of penumbral flow. Look-up tables were calculated to identify the individual thresholds according to the hemispheric reference value.
The individual variation of PW values, even if calculated by deconvolution, remains a major obstacle in quantitative PW imaging and can be significantly improved by a simple MR-based calibration. Easily applicable look-up tables identify the individual best threshold for each PW map to optimize mismatch detection.
[Show abstract][Hide abstract] ABSTRACT: The goal of the study was to investigate the size of the corpus callosum (CC) and its subsegments in relation to total brain volume (TBV) as an empirical indicator of impaired connectivity in autism with special respect to gender. In MRI data sets of 29 adults with high-functioning autism (HFA) and 29 age-, gender- and IQ-matched control subjects, the TBV was measured and the CC was analyzed as a whole and in subsegments employing two different manual segmentation procedures. With respect to diagnosis, there were no significant differences in the dependent variables (CC, CC subsegments, and TBV). With respect to gender, only TBV was significantly increased in males compared with females, resulting in a significantly decreased CC/TBV ratio in males. This finding, however, was independent from gender and can be fully attributed to brain size. Our findings do not support the following hypotheses: (1) a hypothesis of impaired CC in HFA adults as a subgroup of patients with autism spectrum disorders, and (2) the sexual dimorphism hypothesis of the CC.
Psychiatry Research 07/2010; 183(1):38-43. DOI:10.1016/j.pscychresns.2010.04.007 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Perfusion-weighted imaging maps are used to identify hypoperfusion in acute ischemic stroke. We evaluated maps of cerebral blood flow (CBF), cerebral blood volume, mean transit time, and time to peak (TTP) in acute stroke by comparison with positron emission tomography.
Perfusion-weighted imaging and positron emission tomography were performed in 26 patients with acute ischemic stroke (median 18.5 hours after stroke onset, 65 minutes between MRI and positron emission tomography). The perfusion-weighted imaging-derived maps of CBF, cerebral blood volume, mean transit time, and TTP delay were compared with quantitative positron emission tomography CBF. A receiver-operating characteristic curve analysis identified the best perfusion-weighted imaging map and threshold to identify hypoperfusion <20 mL/100 g/min, a widely used measure of penumbral flow.
Individual regression analysis of positron emission tomography CBF and perfusion-weighted imaging values were strong for CBF and TTP delay and weaker for mean transit time and cerebral blood volume, but the pooled analysis showed a large variance. Receiver-operating characteristic curve analysis identified TTP and CBF maps as most predictive (median area under the curve=0.94 and 0.93). Penumbral flow thresholds were <21.7 mL/100 g/min (CBF), <1.5 mL/100 g (cerebral blood volume), >5.3 seconds (mean transit time), and >4.2 seconds (TTP). TTP and CBF maps reached sensitivity/specificity values of 91%/82% and 89%/87%.
In our sample, maps of CBF, TTP, and mean transit time yielded a good estimate of penumbral flow. The performance of TTP maps was equivalent to deconvolution techniques using an arterial input function. For all maps, the application of a predefined threshold is mandatory and calibration studies will enhance their use in acute stroke therapy as well as in clinical stroke trials.
[Show abstract][Hide abstract] ABSTRACT: The best treatment of fulminant or progressive cerebral venous and sinus thrombosis (CVST) despite dose-adjusted heparin remains controversial. Local thrombolysis has been successfully performed in several cases. In cases of impending herniation hemicraniectomy has been suggested as ultima ratio. We describe sequential escalation of therapy in "malignant" CVST.
We report a case of fulminant CVST in whom sequential escalation of therapy with intravenous heparin, local thrombolysis, and hemicraniectomy was necessitated by the progressive clinical course. The patient survived with a relatively good outcome.
This first description on the combined treatment with local thrombolysis and hemicraniectomy illustrates that even in severely affected individuals, therapeutic nihilism is unwarranted and that all available therapeutic options including local thrombolysis and hemicraniectomy should be taken into consideration.
Neurocritical Care 11/2009; 12(1):98-102. DOI:10.1007/s12028-009-9301-1 · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Perfusion-weighted MRI-based maps of cerebral blood flow (CBF(MRI)) are considered a good MRI measure of penumbral flow in acute ischemic stroke but are seldom used in clinical routine due to methodical issues. We validated CBF(MRI) on quantitative CBF measurement by 15O-water positron emission tomography (CBF(PET)). Material and
Comparative CBF(MRI) and CBF(PET) were performed in patients with acute and subacute stroke. In a voxel-based seed-growing technique, predefined CBF(MRI) thresholds (<40, <30, <20, <10 mL/100 g/min) were applied and the resulting volumes were compared with the hypoperfusion volume detected by the penumbral threshold (<20 mL/100 g/min) on CBF(PET). The volumetric comparison was expressed as the C-ratio (volume CBF(MRI)/volume CBF(PET)) to identify the best MRI threshold. The influence of vessel pathology, hypoperfusion size, and time point of imaging was described. The proportion of voxels correctly classified as hypoperfused and the proportion of voxel correctly classified as nonhypoperfused of the best CBF(MRI) threshold was calculated and a Bland-Altman plot illustrated the method-specific differences.
In 24 patients (median time MRI to PET: 68 minutes; 16 patients imaged within 24 hours after stroke), the median volume of hypoperfusion <20 mL/100 g/min (CBF(PET)) was 78.5 cm(3). Median hypoperfusion volume on CBF(MRI) ranged from 245.9 cm(3) (<40 mL/100 g/min) to 35.5 cm(3) (<10 mL/10 g/min). On visual inspection, an excellent qualitative congruence was found. The quantitative congruence was best for the MRI-CBF threshold <20 mL/100 g/min (median C-ratio: 1.0), reaching a proportion of voxels correctly classified as hypoperfused of 76% and a proportion of voxel correctly classified as nonhypoperfused of 96%, but a wide interindividual range (C-ratio 0.3 to 3.5) was found. Ipsilateral vessel pathology, time point of imaging, and size of hypoperfusion did not significantly influence the C-ratio. The Bland-Altman analysis for the volumetric difference of CBF(MRI) and CBF(PET) found a good overall agreement but a large SD.
Hypoperfusion areas below the CBF(PET) penumbral threshold can be well identified by the CBF(MRI) threshold <20 mL/10 g/min at a group level, but a large individual variance (exceeding 20% of volume in nearly half of the patients) could not be explained. Our results support a prudent use of MRI-based quantitative CBF measurement in clinical routine.
[Show abstract][Hide abstract] ABSTRACT: A presentation of all aspects of the dorsolateral medulla oblongata syndrome is clinically very rare to find. In most cases patients present with fragmentary symptoms, e.g. ipsilateral axial lateropulsion, nystagmus, dysarthria, dysphagia or hemiataxia. However, the clinical presentation and lesion anatomy at the level of the medulla oblongata is still unsatisfactory. The aim of this study was to correlate the functional deficit with structural MRI-data.
We included thirteen patients (eight male, five female, mean age 65.5) with medulla oblongata infarction with clinically predominant ipsilateral axial lateropulsion and correlated clinical with structural deficits.
Magnetic resonance imaging lesion mapping demonstrated ipsilateral axial lateropulsion to result from lesions of the spinocerebellar tract, the inferior cerebellar peduncle or the inferior vestibular nucleus. Nystagmus was associated with lesions of the inferior vestibular nucleus, dissociated sensory loss with the spinothalamic tract and hemiataxia with the spinocerebellar tract.
Correlating dysfunction and lesion anatomy is a promising approach to enhance our knowledge on medulla oblongata topography.
European Journal of Neurology 02/2009; 16(2):201-4. DOI:10.1111/j.1468-1331.2008.02381.x · 4.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our purpose was to present our experience regarding embolization of intracranial dural arteriovenous fistulas (DAVFs) with cortical venous reflux using Onyx, a non-adhesive liquid embolic agent.
From January 2006 to December 2007, 16 patients (12 men and 4 women) with a mean age of 61 years (range 42 - 78) with an intracranial DAVF with cortical venous reflux underwent at least one transarterial embolization using Onyx. According to the Cognard classification, 2 lesions were grade V, 5 were grade IV, 6 were grade III, 2 were grade IIa+b, and 1 was grade IIb. The clinical presentation included 5 hemorrhagic deficits, 10 non-hemorrhagic manifestations, and 1 patient was asymptomatic.
Twenty-four embolization sessions were performed in 16 patients with an average of 3 arterial feeders (range 1 - 9) embolized per DAVF. Immediately after embolization, complete occlusion was achieved in 9/16 (56%) patients after the first session. Further postembolization surgical treatment was performed in 3 patients. Partial reperfusion occurred in 1 patient at the time of mean follow-up of 3.7 months (range 0 - 12). Treatment has been completed for 11/16 patients with angiographic cure in 10/11 (91%). An infratentorial bleeding complication related to embolization occurred in one patient with temporary worsening of the patient's gait disturbance. At the time of mean clinical follow-up of 4.5 months (range 0 - 12), no procedure-related permanent morbidity was added to our cohort.
According to our experience, embolization of intracranial DAVFs with cortical venous drainage using Onyx is feasible with promising results, indicating stability at the time of mid-term follow-up. In very complex DAVFs additional embolization material might be necessary, and in some cases surgery is warranted.
RöFo - Fortschritte auf dem Gebiet der R 02/2009; 181(2):129-38. DOI:10.1055/s-2008-1027901 · 1.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Attentional deficits are common symptoms in schizophrenia. Recent evidence suggests that schizophrenic patients show abnormalities in spatial orienting of attention, particularly a deficit of inhibition of return (IOR). IOR is mostly thought to reflect an automatic, inhibitory mechanism protecting the organism from redirecting attention to previously scanned, insignificant locations. Pharmacologic challenges with hallucinogens have been used as models for psychosis.
The aim of this study was to investigate the neural correlates underlying orienting of attention in the human N-methyl-D-aspartic acid antagonist and 5-HT2A agonist models of psychosis.
Fourteen healthy volunteers participated in a randomized, double-blind, cross-over event-related functional magnetic resonance imaging (fMRI) study with dimethyltryptamine (DMT) and S-ketamine. We administered a covert orienting of attention task with nonpredictive peripheral cues, and we scanned the subjects on two separate days at least 14 days apart with a placebo and a verum condition on each day.
DMT, but not S-ketamine, slowed down reaction times significantly. IOR was blunted after DMT, but not after S-ketamine. Relative to placebo, S-ketamine increased activation in the IOR condition in the right superior frontal gyrus, left superior temporal gyrus, and right midfrontal frontal gyrus.
The discrepancy between the behavioral and functional imaging outcome indicates that pharmacological fMRI might be a sensitive tool to detect drug-modulated blood oxygenation level-dependent signal changes in the absence of behavioral abnormalities. Our findings might help to further clarify the contradictory findings of IOR in schizophrenic patients and might, thus, shed more light on possible differential pathomechanisms of schizophrenic symptoms.